Low viscosity liquid nicotine formulation

ABSTRACT

A liquid nicotine formulation for an aerosol-generating system is provided, the liquid nicotine formulation including: glycerine and having a viscosity at 20° C. of less than or equal to about 20 mPa·s, wherein the liquid nicotine formulation being a substantially uncaffeinated liquid nicotine formulation, and the liquid nicotine formulation having a glycerine content of greater than or equal to about 6 percent by weight. A cartridge for an aerosol-generating system, and an aerosol-generating system, are also provided.

The invention relates to a liquid nicotine formulation for use in anaerosol-generating system. In particular, the invention relates to aliquid nicotine formulation for use in an aerosol-generating systemcomprising a non-thermal atomiser. The invention also relates to acartridge for an aerosol-generating system comprising the liquidnicotine formulation and an aerosol-generating system comprising theliquid nicotine formulation and an atomiser configured to generate anaerosol from the liquid nicotine formulation.

Aerosol-generating systems for delivering nicotine to a user thatcomprise an atomiser configured to generate an inhalable aerosol from aliquid nicotine formulation are known. Some known aerosol-generatingsystems comprise a thermal atomiser such as an electric heater that isconfigured to heat and vaporise the liquid nicotine formulation togenerate an aerosol. Other known aerosol-generating systems comprise anon-thermal atomiser that is configured to generate an aerosol from theliquid nicotine formulation using, for example, impinging jet,ultrasonic or vibrating mesh technologies.

In such aerosol-generating systems, pulmonary delivery of the inhalableaerosol generated from the liquid nicotine formulation is important foruser palatability and satisfaction. Nicotine adsorption through thepulmonary alveoli is rapid and efficient. By contrast, nicotineadsorption in the upper airways is slower and less efficient. Nicotineadsorption in the upper airways may also undesirably be perceived by auser as having a sensorial harshness and induce mouth and throatirritation.

The lung deposition characteristics and hence efficacy of the inhalableaerosol generated from the liquid nicotine formulation depend on theparticle or droplet size of the aerosol. Typically, a small particle ordroplet size is desired to maximise pulmonary nicotine delivery andretention. In particular, it is believed that a particle or droplet sizeof less than or equal to about 5 micrometres in diameter may bedesirable to maximise pulmonary delivery.

To enhance pulmonary nicotine delivery and retention, it would bedesirable to provide a liquid nicotine formulation for use in anaerosol-generating system that facilitates generation of an aerosolhaving a small droplet size. For example, it would be desirable toprovide a liquid nicotine formulation for use in an aerosol-generatingsystem that facilitates generation of an aerosol having a particle ordroplet size of less than or equal to about 5 micrometres in diameter.

According to the invention there is provided a liquid nicotineformulation for use in an aerosol-generating system, the liquid nicotineformulation having a viscosity at 20° C. of less than or equal to about20 millipascal seconds (mPa·s).

According to the invention there is also provided a cartridge for use inan aerosol-generating system, the cartridge containing a liquid nicotineformulation having a viscosity at 20° C. of less than or equal to about20 millipascal seconds (mPa·s).

According to the invention there is further provided anaerosol-generating system comprising: a liquid nicotine formulationhaving a viscosity at 20° C. of less than or equal to about 20millipascal seconds (mPa·s); and an atomiser configured to generate anaerosol from the liquid nicotine formulation.

As used herein with reference to the invention, the term “liquidnicotine formulation” describes a liquid formulation comprisingnicotine.

As used herein with reference to the invention, the term “nicotine”describes nicotine, nicotine base or a nicotine salt. In embodiments inwhich the liquid nicotine formulation comprises a nicotine base or anicotine salt, the amounts of nicotine recited herein are the amount offree base nicotine or amount of protonated nicotine, respectively.

When used in an aerosol-generating system, the low viscosity of theliquid nicotine formulation according to the invention facilitatesgeneration of an inhalable aerosol having a small particle or dropletsize. This may advantageously enhance pulmonary nicotine delivery andretention.

As discussed further below, use of the liquid nicotine formulationaccording to the invention in an aerosol-generating system comprising anon-thermal atomiser is particularly advantageous.

The liquid nicotine formulation may comprise natural nicotine orsynthetic nicotine.

Unless stated otherwise, viscosity values recited herein are theviscosity of an 8 millilitre (mL) sample volume of liquid nicotineformulation measured using a Brookfield RVDV-II +Pro viscometer fittedwith a Brookfield Small Sample Adapter comprising a cylindrical SC4-13RSample Chamber and a cylindrical SC4-21 Spindle at a speed of 100revolutions per minute (rpm).

The liquid nicotine formulation may have a viscosity at 20° C. of lessthan or equal to about 18 mPa·s or less than or equal to about 16 mPa·s.

Preferably, the liquid nicotine formulation has a viscosity at 20° C. ofless than or equal to about 14 mPa·s. More preferably, the liquidnicotine formulation has a viscosity at 20° C. of less than or equal toabout 12 mPa·s. For example, the liquid nicotine formulation may have aviscosity at 20° C. of less than or equal to about 10 mPa·s.

Preferably, the liquid nicotine formulation has a viscosity at 20° C. ofgreater than or equal to about 0.75 mPa·s. More preferably, the liquidnicotine formulation has a viscosity at 20° C. of greater than or equalto about 1 mPa·s. For example, the liquid nicotine formulation may havea viscosity at 20° C. of greater than or equal to about 1.25 mPa·s,greater than or equal to about 1.5 mPa·s or greater than or equal toabout 1.75 mPa·s.

The liquid nicotine formulation may have a viscosity at 20° C. ofbetween about 0.75 mPa·s and about 18 mPa·s. For example, the liquidnicotine formulation may have a viscosity at 20° C. of between about 1mPa·s and about 18 mPa·s, between about 1.25 mPa·s and about 18 mPa·s,between about 1.5 mPa·s and about 18 mPa·s or between about 1.75 mPa·sand about 18 mPa·s.

The liquid nicotine formulation may have a viscosity at 20° C. ofbetween about 0.75 mPa·s and about 16 mPa·s. For example, the liquidnicotine formulation may have a viscosity at 20° C. of between about 1mPa·s and about 16 mPa·s, between about 1.25 mPa·s and about 16 mPa·s,between about 1.5 mPa·s and about 16 mPa·s or between about 1.75 mPa·sand about 16 mPa·s.

Preferably, the liquid nicotine formulation has a viscosity at 20° C. ofbetween about 0.75 mPa·s and about 14 mPa·s. For example, the liquidnicotine formulation may have a viscosity at 20° C. of between about 1mPa·s and about 14 mPa·s, between about 1.25 mPa·s and about 14 mPa·s,between about 1.5 mPa·s and about 14 mPa·s or between about 1.75 mPa·sand about 14 mPa·s.

More preferably, the liquid nicotine formulation has a viscosity at 20°C. of between about 0.75 mPa·s and about 12 mPa·s. For example, theliquid nicotine formulation may have a viscosity at 20° C. of betweenabout 1 mPa·s and about 12 mPa·s, between about 1.25 mPa·s and about 12mPa·s, between about 1.5 mPa·s and about 12 mPa·s or between about 1.75mPa·s and about 12 mPa·s.

The liquid nicotine formulation may have a viscosity at 20° C. ofbetween about 0.75 mPa·s and about 10 mPa·s. For example, the liquidnicotine formulation may have a viscosity at 20° C. of between about 1mPa·s and about 10 mPa·s, between about 1.25 mPa·s and about 10 mPa·s,between about 1.5 mPa·s and about 10 mPa·s or between about 1.75 mPa·sand about 10 mPa·s.

The liquid nicotine formulation may have a nicotine content of greaterthan or equal to about 0.5 percent by weight.

Unless stated otherwise, percentages by weight of components of theliquid nicotine formulation recited herein are based on the total weightof the liquid nicotine formulation.

Preferably, the liquid nicotine formulation has a nicotine content ofgreater than or equal to about 1 percent by weight. More preferably, theliquid nicotine formulation has a nicotine content of greater than orequal to about 1.5 percent by weight.

The liquid nicotine formulation may have a nicotine content of less thanor equal to about 10 percent by weight. The liquid nicotine formulationmay have a nicotine content of less than or equal to about 8 percent byweight.

Preferably, the liquid nicotine formulation has a nicotine content ofless than or equal to about 5 percent by weight. More preferably, theliquid nicotine formulation has a nicotine content of less than or equalto about 3 percent by weight.

The liquid nicotine formulation may have a nicotine content of betweenabout 0.5 percent by weight and about 10 percent by weight. For example,the liquid nicotine formulation may have a nicotine content of betweenabout 0.5 percent by weight and about 8 percent by weight, between about0.5 percent by weight and about 5 percent by weight or between about 0.5percent by weight and about 3 percent by weight.

Preferably, the liquid nicotine formulation has a nicotine content ofbetween about 1 percent by weight and about 10 percent by weight. Forexample, the liquid nicotine formulation may have a nicotine content ofbetween about 1 percent by weight and about 8 percent by weight, betweenabout 1 percent by weight and about 5 percent by weight or between about1 percent by weight and about 3 percent by weight.

More preferably, the liquid nicotine formulation has a nicotine contentof between about 1.5 percent by weight and about 10 percent by weight.For example, the liquid nicotine formulation may have a nicotine contentof between about 1.5 percent by weight and about 8 percent by weight,between about 1.5 percent by weight and about 5 percent by weight orbetween about 1.5 percent by weight and about 3 percent by weight.

Preferably, the liquid nicotine formulation comprises water.

The liquid nicotine formulation may have a water content of greater thanor equal to about 10 percent by weight, greater than or equal to about15 percent by weight or greater than or equal to about 20 percent byweight.

Preferably, the liquid nicotine formulation has a water content ofgreater than or equal to about 25 percent by weight. More preferably,the liquid nicotine formulation has a water content of greater than orequal to about 30 percent by weight. For example, the liquid nicotineformulation may have a water content of greater than or equal to about35 percent by weight or greater than or equal to about 40 percent byweight.

Inclusion of at least about 25 percent by weight water advantageouslyfacilitates attainment of a liquid nicotine formulation having aviscosity at 20° C. of less than or equal to about 20 mPa·s.

Preferably, the liquid nicotine formulation has a water content of lessthan or equal to about 90 percent by weight. More preferably, the liquidnicotine formulation has a water content of less than or equal to about85 percent by weight. For example, the liquid nicotine formulation mayhave a water content of less than or equal to about 80 percent byweight, less than or equal to about 75 percent by weight, less than orequal to about 70 percent by weight or less than or equal to about 65percent by weight.

The liquid nicotine formulation may have a water content of betweenabout 10 percent by weight and about 90 percent by weight. For example,the liquid nicotine formulation may have a water content of betweenabout 10 percent by weight and about 85 percent by weight, between about10 percent by weight and about 80 percent by weight, between about 10percent by weight and about 75 percent by weight, between about 10percent by weight and about 70 percent by weight or between about 10percent by weight and about 65 percent by weight.

The liquid nicotine formulation may have a water content of betweenabout 15 percent by weight and about 90 percent by weight. For example,the liquid nicotine formulation may have a water content of betweenabout 15 percent by weight and about 85 percent by weight, between about15 percent by weight and about 80 percent by weight, between about 15percent by weight and about 75 percent by weight, between about 15percent by weight and about 70 percent by weight, between about 15percent by weight and about 65 percent by weight.

The liquid nicotine formulation may have a water content of betweenabout 20 percent by weight and about 90 percent by weight. For example,the liquid nicotine formulation may have a water content of betweenabout 20 percent by weight and about 85 percent by weight, between about20 percent by weight and about 80 percent by weight, between about 20percent by weight and about 75 percent by weight, between about 20percent by weight and about 70 percent by weight or between about 20percent by weight and about 65 percent by weight.

Preferably, the liquid nicotine formulation has a water content ofbetween about 25 percent by weight and about 90 percent by weight. Forexample, the liquid nicotine formulation may have a water content ofbetween about 25 percent by weight and about 85 percent by weight,between about 25 percent by weight and about 80 percent by weight,between about 25 percent by weight and about 75 percent by weight,between about 25 percent by weight and about 70 percent by weight orbetween about 25 percent by weight and about 65 percent by weight.

More preferably, the liquid nicotine formulation has a water content ofbetween about 30 percent by weight and about 90 percent by weight. Forexample, the liquid nicotine formulation may have a water content ofbetween about 30 percent by weight and about 85 percent by weight,between about 30 percent by weight and about 80 percent by weight,between about 30 percent by weight and about 75 percent by weight,between about 30 percent by weight and about 70 percent by weight orbetween about 30 percent by weight and about 65 percent by weight.

The liquid nicotine formulation may have a water content of betweenabout 35 percent by weight and about 90 percent by weight. For example,the liquid nicotine formulation may have a water content of betweenabout 35 percent by weight and about 85 percent by weight, between about35 percent by weight and about 80 percent by weight, between about 35percent by weight and about 75 percent by weight, between about 35percent by weight and about 70 percent by weight or between about 35percent by weight and about 65 percent by weight.

The liquid nicotine formulation may have a water content of betweenabout 40 percent by weight and about 90 percent by weight. For example,the liquid nicotine formulation may have a water content of betweenabout 40 percent by weight and about 85 percent by weight, between about40 percent by weight and about 80 percent by weight, between about 40percent by weight and about 75 percent by weight, between about 40percent by weight and about 70 percent by weight or between about 40percent by weight and about 65 percent by weight.

Preferably, the liquid nicotine formulation comprises one or morewater-miscible solvents.

As used herein with reference to the invention, the term “water-misciblesolvent” describes a compound other than water or an organic acid thatis liquid at 20° C. and mixes with water in all proportions to form ahomogenous solution.

More preferably, the liquid nicotine formulation comprises water and oneor more water-miscible solvents.

In combination the water and one or more water-miscible solvents mayadvantageously help to dissolve and stabilise polar components and ioniccomponents of the liquid nicotine formulation.

Preferably, the liquid nicotine formulation has a water-miscible solventcontent of greater than or equal to about 5 percent by weight. Morepreferably, the liquid nicotine formulation has a water-miscible solventcontent of greater than or equal to about 10 percent by weight. Forexample, the liquid nicotine formulation may have a water-misciblesolvent content of greater than or equal to about 15 percent by weight,greater than or equal to about 20 percent by weight or greater than orequal to about 25 percent by weight.

The liquid nicotine formulation may have a water-miscible solventcontent of less than or equal to about 80 percent by weight, less thanor equal to about 75 percent by weight or less than or equal to about 70percent by weight.

Preferably, the liquid nicotine formulation has a water-miscible solventcontent of less than or equal to about 60 percent by weight. Morepreferably, the liquid nicotine formulation has a water-miscible solventcontent of less than or equal to about 50 percent by weight. Forexample, the liquid nicotine formulation may have a water-misciblesolvent content of less than or equal to about 40 percent by weight.

The liquid nicotine formulation may have a water-miscible solventcontent of between about 5 percent by weight and about 80 percent byweight, between about 5 percent by weight and about 75 percent by weightor between about 5 percent by weight and about 70 percent by weight.

Preferably, the liquid nicotine formulation has a water-miscible solventcontent of between about 5 percent by weight and about 60 percent byweight. For example, the liquid nicotine formulation may have awater-miscible solvent content of between about 5 percent by weight andabout 50 percent by weight or between about 5 percent by weight andabout 40 percent by weight.

The liquid nicotine formulation may have a water-miscible solventcontent of between about 10 percent by weight and about 80 percent byweight, between about 10 percent by weight and about 75 percent byweight or between about 10 percent by weight and about 70 percent byweight.

More preferably, the liquid nicotine formulation has a water-misciblesolvent content of between about 10 percent by weight and about 60percent by weight. For example, the liquid nicotine formulation may havea water-miscible solvent content of between about 10 percent by weightand about 50 percent by weight or between about 10 percent by weight andabout 40 percent by weight.

The liquid nicotine formulation may have a water-miscible solventcontent of between about 15 percent by weight and about 80 percent byweight, between about 15 percent by weight and about 75 percent byweight, between about 15 percent by weight and about 70 percent byweight, between about 15 percent by weight and about 60 percent byweight, between about 15 percent by weight and about 50 percent byweight or between about 15 percent by weight and about 40 percent byweight.

The liquid nicotine formulation may have a water-miscible solventcontent of between about 20 percent by weight and about 80 percent byweight, between about 20 percent by weight and about 75 percent byweight, between about 20 percent by weight and about 70 percent byweight, between about 20 percent by weight and about 60 percent byweight, between about 20 percent by weight and about 50 percent byweight or between about 20 percent by weight and about 40 percent byweight.

The liquid nicotine formulation may have a water-miscible solventcontent of between about 25 percent by weight and about 80 percent byweight, between about 25 percent by weight and about 75 percent byweight, between about 25 percent by weight and about 70 percent byweight, between about 25 percent by weight and about 60 percent byweight, between about 25 percent by weight and about 50 percent byweight or between about 25 percent by weight and about 40 percent byweight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible solvents, the liquid nicotine formulationmay have a combined water and water-miscible solvent content of greaterthan or equal to about 50 percent by weight, greater than or equal toabout 55 percent by weight, greater than or equal to about 60 percent byweight, greater than or equal to about 65 percent by weight or greaterthan or equal to about 70 percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible solvents, preferably the liquid nicotineformulation has a combined water and water-miscible solvent content ofgreater than or equal to about 75 percent by weight. More preferably,the liquid nicotine formulation has a combined water and water-misciblesolvent content of greater than or equal to 80 percent by weight. Mostpreferably, the liquid nicotine formulation has a combined water andwater-miscible solvent content of greater than or equal to about 85percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible solvents, preferably the weight percentwater content of the liquid nicotine formulation is at least about 0.8times the weight percent water-miscible solvent content of the liquidnicotine formulation. More preferably the weight percent water contentof the liquid nicotine formulation is at least about 1.5 times theweight percent water-miscible solvent content of the liquid nicotineformulation.

That is, preferably the ratio of the weight percent water content to theweight percent water-miscible solvent content of the liquid nicotineformulation is greater than or equal to about 0.8, more preferablygreater than or equal to about 1.5.

The weight percent water content of the liquid nicotine formulation maybe at least about 2 times the weight percent water-miscible solventcontent of the liquid nicotine formulation, at least about 3 times theweight percent water-miscible solvent content of the liquid nicotineformulation, at least about 4 times the weight percent water-misciblesolvent content of the liquid nicotine formulation or at least about 5times the weight percent water-miscible solvent content of the liquidnicotine formulation.

That is, the ratio of the weight percent water content to the weightpercent water-miscible solvent content of the liquid nicotineformulation may be greater than or equal to about 2, greater than orequal to about 3, greater than or equal to about 4 or greater than orequal to about 5.

Preferably the weight percent water content of the liquid nicotineformulation is less than or equal to about 9 times the weight percentwater-miscible solvent of the liquid nicotine formulation. Morepreferably, the weight percent water content of the liquid nicotineformulation is less than or equal to about 8 times the weight percentwater-miscible solvent content of the liquid nicotine formulation.

That is, preferably the ratio of the weight percent water content to theweight percent water-miscible solvent content of the liquid nicotineformulation is less than or equal to about 9, more preferably less thanor equal to about 8.

The weight percent water content of the liquid nicotine formulation maybe less than or equal to about 7 times the weight percent water-misciblesolvent content of the liquid nicotine formulation.

That is, the ratio of the weight percent water content to the weightpercent water-miscible solvent content of the liquid nicotineformulation may be less than or equal to about 7.

Preferably, the weight percent water content of the liquid nicotineformulation is between about 0.8 times and about 9 times the weightpercent water-miscible solvent content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 0.8 times and about 8 timesthe weight percent water-miscible solvent content of the liquid nicotineformulation or between about 0.8 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

More preferably, the weight percent water content of the liquid nicotineformulation is between about 1.5 times and about 9 times the weightpercent water-miscible solvent content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 1.5 times and about 8 timesthe weight percent water-miscible solvent content of the liquid nicotineformulation or between about 1.5 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

The weight percent water content of the liquid nicotine formulation maybe between about 2 times and about 9 times the weight percentwater-miscible solvent content of the liquid nicotine formulation. Forexample, the weight percent water content of the liquid nicotineformulation may be between about 2 times and about 8 times the weightpercent water-miscible solvent content of the liquid nicotineformulation or between about 2 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

The weight percent water content of the liquid nicotine formulation maybe between about 3 times and about 9 times the weight percentwater-miscible solvent content of the liquid nicotine formulation. Forexample, the weight percent water content of the liquid nicotineformulation may be between about 3 times and about 8 times the weightpercent water-miscible solvent content of the liquid nicotineformulation or between about 3 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

The weight percent water content of the liquid nicotine formulation maybe between about 4 times and about 9 times the weight percentwater-miscible solvent content of the liquid nicotine formulation. Forexample, the weight percent water content of the liquid nicotineformulation may be between about 4 times and about 8 times the weightpercent water-miscible solvent content of the liquid nicotineformulation or between about 4 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

The weight percent water content of the liquid nicotine formulation maybe between about 5 times and about 9 times the weight percentwater-miscible solvent content of the liquid nicotine formulation. Forexample, the weight percent water content of the liquid nicotineformulation may be between about 5 times and about 8 times the weightpercent water-miscible solvent content of the liquid nicotineformulation or between about 5 times and about 7 times the weightpercent water-miscible solvent content of the liquid nicotineformulation.

The one or more water-miscible solvents may be one or morewater-miscible polyhydric alcohols.

Preferably, the liquid nicotine formulation comprises one or morewater-miscible polyhydric alcohols.

As used herein with reference to the invention, the term “water-misciblepolyhydric alcohol” describes a polyhydric alcohol that is liquid at 20°C. and mixes with water in all proportions to form a homogenoussolution.

More preferably, the liquid nicotine formulation comprises water and oneor more water-miscible polyhydric alcohols.

Preferably, the liquid nicotine formulation has a water-misciblepolyhydric alcohol content of greater than or equal to about 5 percentby weight. More preferably, the liquid nicotine formulation has awater-miscible polyhydric alcohol content of greater than or equal toabout 10 percent by weight. For example, the liquid nicotine formulationmay have a water-miscible polyhydric alcohol content of greater than orequal to about 15 percent by weight, greater than or equal to about 20percent by weight or greater than or equal to about 25 percent byweight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of less than or equal to about 80 percent by weight,less than or equal to about 75 percent by weight or less than or equalto about 70 percent by weight.

Preferably, the liquid nicotine formulation has a water-misciblepolyhydric alcohol content of less than or equal to about 60 percent byweight. More preferably, the liquid nicotine formulation has awater-miscible polyhydric alcohol content of less than or equal to about50 percent by weight. For example, the liquid nicotine formulation mayhave a water-miscible polyhydric alcohol content of less than or equalto about 40 percent by weight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of between about 5 percent by weight and about 80percent by weight, between about 5 percent by weight and about 75percent by weight or between about 5 percent by weight and about 70percent by weight.

Preferably, the liquid nicotine formulation has a water-misciblepolyhydric alcohol content of between about 5 percent by weight andabout 60 percent by weight. For example, the liquid nicotine formulationmay have a water-miscible polyhydric alcohol content of between about 5percent by weight and about 50 percent by weight or between about 5percent by weight and about 40 percent by weight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of between about 10 percent by weight and about 80percent by weight, between about 10 percent by weight and about 75percent by weight or between about 10 percent by weight and about 70percent by weight.

More preferably, the liquid nicotine formulation has a water-misciblepolyhydric alcohol content of between about 10 percent by weight andabout 60 percent by weight. For example, the liquid nicotine formulationmay have a water-miscible polyhydric alcohol content of between about 10percent by weight and about 50 percent by weight or between about 10percent by weight and about 40 percent by weight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of between about 15 percent by weight and about 80percent by weight, between about 15 percent by weight and about 75percent by weight, between about 15 percent by weight and about 70percent by weight, between about 15 percent by weight and about 60percent by weight, between about 15 percent by weight and about 50percent by weight or between about 15 percent by weight and about 40percent by weight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of between about 20 percent by weight and about 80percent by weight, between about 20 percent by weight and about 75percent by weight, between about 20 percent by weight and about 70percent by weight, between about 20 percent by weight and about 60percent by weight, between about 20 percent by weight and about 50percent by weight or between about 20 percent by weight and about 40percent by weight.

The liquid nicotine formulation may have a water-miscible polyhydricalcohol content of between about 25 percent by weight and about 80percent by weight, between about 25 percent by weight and about 75percent by weight, between about 25 percent by weight and about 70percent by weight, between about 25 percent by weight and about 60percent by weight, between about 25 percent by weight and about 50percent by weight or between about 25 percent by weight and about 40percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible polyhydric alcohols, the liquid nicotineformulation may have a combined water and water-miscible polyhydricalcohol content of greater than or equal to about 50 percent by weight,greater than or equal to about 55 percent by weight, greater than orequal to about 60 percent by weight, greater than or equal to about 65percent by weight or greater than or equal to about 70 percent byweight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible polyhydric alcohols, preferably theliquid nicotine formulation has a combined water and water-misciblepolyhydric alcohol content of greater than or equal to about 75 percentby weight. More preferably, the liquid nicotine formulation has acombined water and water-miscible polyhydric alcohol content of greaterthan or equal to 80 percent by weight. Most preferably, the liquidnicotine formulation has a combined water and water-miscible polyhydricalcohol content of greater than or equal to about 85 percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible polyhydric alcohols, preferably theweight percent water content of the liquid nicotine formulation is atleast about 0.8 times the weight percent water-miscible polyhydricalcohol content of the liquid nicotine formulation. More preferably theweight percent water content of the liquid nicotine formulation is atleast about 1.5 times the weight percent water-miscible polyhydricalcohol content of the liquid nicotine formulation.

That is, preferably the ratio of the weight percent water content to theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation is greater than or equal to about 0.8, morepreferably greater than or equal to about 1.5.

The weight percent water content of the liquid nicotine formulation maybe at least about 2 times the weight percent water-miscible polyhydricalcohol content of the liquid nicotine formulation, at least about 3times the weight percent water-miscible polyhydric alcohol content ofthe liquid nicotine formulation, at least about 4 times the weightpercent water-miscible polyhydric alcohol content of the liquid nicotineformulation or at least about 5 times the weight percent water-misciblepolyhydric alcohol content of the liquid nicotine formulation.

That is, the ratio of the weight percent water content to the weightpercent water-miscible polyhydric alcohol content of the liquid nicotineformulation may be greater than or equal to about 2, greater than orequal to about 3, greater than or equal to about 4 or greater than orequal to about 5.

Preferably the weight percent water content of the liquid nicotineformulation is less than or equal to about 9 times the weight percentwater-miscible polyhydric alcohol of the liquid nicotine formulation.More preferably, the weight percent water content of the liquid nicotineformulation is less than or equal to about 8 times the weight percentwater-miscible polyhydric alcohol content of the liquid nicotineformulation.

That is, preferably the ratio of the weight percent water content to theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation is less than or equal to about 9, more preferablyless than or equal to about 8.

The weight percent water content of the liquid nicotine formulation maybe less than or equal to about 7 times the weight percent water-misciblepolyhydric alcohol content of the liquid nicotine formulation.

That is, the ratio of the weight percent water content to the weightpercent water-miscible polyhydric alcohol content of the liquid nicotineformulation may be less than or equal to about 7.

Preferably, the weight percent water content of the liquid nicotineformulation is between about 0.8 times and about 9 times the weightpercent water-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 0.8 times and about 8 timesthe weight percent water-miscible polyhydric alcohol content of theliquid nicotine formulation or between about 0.8 times and about 7 timesthe weight percent water-miscible polyhydric alcohol content of theliquid nicotine formulation.

More preferably, the weight percent water content of the liquid nicotineformulation is between about 1.5 times and about 9 times the weightpercent water-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 1.5 times and about 8 timesthe weight percent water-miscible polyhydric alcohol content of theliquid nicotine formulation or between about 1.5 times and about 7 timesthe weight percent water-miscible polyhydric alcohol content of theliquid nicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 2 times and about 9 times the weight percentwater-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 2 times and about 8 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation or between about 2 times and about 7 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 3 times and about 9 times the weight percentwater-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 3 times and about 8 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation or between about 3 times and about 7 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 4 times and about 9 times the weight percentwater-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 4 times and about 8 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation or between about 4 times and about 7 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 5 times and about 9 times the weight percentwater-miscible polyhydric alcohol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 5 times and about 8 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation or between about 5 times and about 7 times theweight percent water-miscible polyhydric alcohol content of the liquidnicotine formulation.

Preferably, the liquid nicotine formulation comprises one or morewater-miscible polyhydric alcohols selected from the group consisting of1,3-butanediol, glycerine, propylene glycol, and triethylene glycol.

More preferably, the liquid nicotine formulation comprises water and oneor more water-miscible polyhydric alcohols selected from the groupconsisting of 1,3-butanediol, glycerine, propylene glycol, andtriethylene glycol.

Preferably, the liquid nicotine formulation comprises glycerine.

More preferably, the liquid nicotine formulation comprises vegetableglycerine.

Preferably, the liquid nicotine formulation comprises water andglycerine.

More preferably, the liquid nicotine formulation comprises water andvegetable glycerine.

Preferably, the liquid nicotine formulation comprises glycerine andpropylene glycol.

More preferably, the liquid nicotine formulation comprises vegetableglycerine and propylene glycol.

Preferably, the liquid nicotine formulation comprises water, glycerineand propylene glycol.

More preferably, the liquid nicotine formulation comprises water,vegetable glycerine and propylene glycol.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, preferably the liquid nicotineformulation has a combined glycerine and propylene glycol content ofgreater than or equal to about 5 percent by weight. More preferably, theliquid nicotine formulation has a combined glycerine and propyleneglycol content of greater than or equal to about 10 percent by weight.For example, the liquid nicotine formulation may have a combinedglycerine and propylene glycol content of greater than or equal to about15 percent by weight, greater than or equal to about 20 percent byweight or greater than or equal to about 25 percent by weight.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, the liquid nicotine formulationmay have a combined glycerine and propylene glycol content of less thanor equal to about 80 percent by weight, less than or equal to about 75percent by weight or less than or equal to about 70 percent by weight.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, preferably the liquid nicotineformulation has a combined glycerine and propylene glycol content ofless than or equal to about 60 percent by weight. More preferably, theliquid nicotine formulation has a combined glycerine and propyleneglycol content of less than or equal to about 50 percent by weight. Forexample, the liquid nicotine formulation may have a combined glycerineand propylene glycol content of less than or equal to about 40 percentby weight.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, the liquid nicotine formulationmay have a combined glycerine and propylene glycol content of betweenabout 5 percent by weight and about 80 percent by weight, between about5 percent by weight and about 75 percent by weight or between about 5percent by weight and about 70 percent by weight.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, preferably the liquid nicotineformulation has a combined glycerine and propylene glycol content ofbetween about 5 percent by weight and about 60 percent by weight. Forexample, the liquid nicotine formulation may have a combined glycerineand propylene glycol content of between about 5 percent by weight andabout 50 percent by weight or between about 5 percent by weight andabout 40 percent by weight.

In embodiments in which the liquid nicotine formulation comprises one orboth of glycerine and propylene glycol, the liquid nicotine formulationmay have a combined glycerine and propylene glycol content of betweenabout 10 percent by weight and about 80 percent by weight, between about10 percent by weight and about 75 percent by weight or between about 10percent by weight and about 70 percent by weight.

More preferably, the liquid nicotine formulation has a combinedglycerine and propylene glycol content of between about 10 percent byweight and about 60 percent by weight. For example, the liquid nicotineformulation may have a combined glycerine and propylene glycol contentof between about 10 percent by weight and about 50 percent by weight orbetween about 10 percent by weight and about 40 percent by weight.

The liquid nicotine formulation may have a combined glycerine andpropylene glycol content of between about 15 percent by weight and about80 percent by weight, between about 15 percent by weight and about 75percent by weight, between about 15 percent by weight and about 70percent by weight, between about 15 percent by weight and about 60percent by weight, between about 15 percent by weight and about 50percent by weight or between about 15 percent by weight and about 40percent by weight.

The liquid nicotine formulation may have a combined glycerine andpropylene glycol content of between about 20 percent by weight and about80 percent by weight, between about 20 percent by weight and about 75percent by weight, between about 20 percent by weight and about 70percent by weight, between about 20 percent by weight and about 60percent by weight, between about 20 percent by weight and about 50percent by weight or between about 20 percent by weight and about 40percent by weight.

The liquid nicotine formulation may have a combined glycerine andpropylene glycol content of between about 25 percent by weight and about80 percent by weight, between about 25 percent by weight and about 75percent by weight, between about 25 percent by weight and about 70percent by weight, between about 25 percent by weight and about 60percent by weight, between about 25 percent by weight and about 50percent by weight or between about 25 percent by weight and about 40percent by weight.

Preferably, the liquid nicotine formulation has a glycerine content ofgreater than or equal to about 5 percent by weight.

More preferably, the liquid nicotine formulation has a glycerine contentof greater than or equal to about 6 percent by weight. For example, theliquid nicotine formulation may have a glycerine content of greater thanor equal to about 7 percent by weight or greater than or equal to about8 percent by weight.

The liquid nicotine formulation may have a glycerine content of lessthan or equal to about 80 percent by weight or less than or equal toabout 75 percent by weight.

Preferably, the liquid nicotine formulation has a glycerine content ofless than or equal to about 70 percent by weight. More preferably, theliquid nicotine formulation has a glycerine content of less than orequal to about 60 percent by weight. For example, the liquid nicotineformulation may have a glycerine content of less than or equal to about50 percent by weight or less than or equal to about 40 percent byweight.

Preferably, the liquid nicotine formulation has a glycerine content ofbetween about 5 percent by weight and about 70 percent by weight. Forexample, the liquid nicotine formulation may have a glycerine content ofbetween about 5 percent by weight and about 60 percent by weight,between about 5 percent by weight and about 50 percent by weight orbetween about 5 percent by weight and about 40 percent by weight.

More preferably, the liquid nicotine formulation has a glycerine contentof between about 6 percent by weight and about 70 percent by weight. Forexample, the liquid nicotine formulation may have a glycerine content ofbetween about 6 percent by weight and about 60 percent by weight,between about 6 percent by weight and about 50 percent by weight orbetween about 6 percent by weight and about 40 percent by weight.

The liquid nicotine formulation may have a glycerine content of betweenabout 7 percent by weight and about 70 percent by weight, between about7 percent by weight and about 60 percent by weight, between about 7percent by weight and about 50 percent by weight or between about 7percent by weight and about 40 percent by weight.

The liquid nicotine formulation may have a glycerine content of betweenabout 8 percent by weight and about 70 percent by weight, between about8 percent by weight and about 60 percent by weight, between about 8percent by weight and about 50 percent by weight or between about 8percent by weight and about 40 percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand water and one or both of glycerine and propylene glycol, the liquidnicotine formulation may have a combined water, glycerine and propyleneglycol content of greater than or equal to about 50 percent by weight,greater than or equal to about 55 percent by weight, greater than orequal to about 60 percent by weight, greater than or equal to about 65percent by weight or greater than or equal to about 70 percent byweight.

In embodiments in which the liquid nicotine formulation comprises waterand one or both of glycerine and propylene glycol, preferably the liquidnicotine formulation has a combined water, glycerine and propyleneglycol content of greater than or equal to about 75 percent by weight.More preferably, the liquid nicotine formulation has a combined water,glycerine and propylene glycol content of greater than or equal to 80percent by weight. Most preferably, the liquid nicotine formulation hasa combined water, glycerine and propylene glycol content of greater thanor equal to about 85 percent by weight.

In embodiments in which the liquid nicotine formulation comprises waterand one or both of glycerine and propylene glycol, preferably the weightpercent water content of the liquid nicotine formulation is at leastabout 0.8 times the combined weight percent glycerine and propyleneglycol content of the liquid nicotine formulation. More preferably theweight percent water content of the liquid nicotine formulation is atleast about 1.5 times the combined weight percent glycerine andpropylene glycol content of the liquid nicotine formulation.

That is, preferably the ratio of the weight percent water content to thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation is greater than or equal to about 0.8, morepreferably greater than or equal to about 1.5.

The weight percent water content of the liquid nicotine formulation maybe at least about 2 times the combined weight percent glycerine andpropylene glycol content of the liquid nicotine formulation, at leastabout 3 times the combined weight percent glycerine and propylene glycolcontent of the liquid nicotine formulation, at least about 4 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation or at least about 5 times the combinedweight percent glycerine and propylene glycol content of the liquidnicotine formulation.

That is, the ratio of the weight percent water content to the combinedweight percent glycerine and propylene glycol content of the liquidnicotine formulation may be greater than or equal to about 2, greaterthan or equal to about 3, greater than or equal to about 4 or greaterthan or equal to about 5.

Preferably the weight percent water content of the liquid nicotineformulation is less than or equal to about 9 times the combined weightpercent glycerine and propylene glycol content of the liquid nicotineformulation. More preferably, the weight percent water content of theliquid nicotine formulation is less than or equal to about 8 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation.

That is, preferably the ratio of the weight percent water content to thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation is less than or equal to about 9, morepreferably less than or equal to about 8.

The weight percent water content of the liquid nicotine formulation maybe less than or equal to about 7 times the combined weight percentglycerine and propylene glycol content of the liquid nicotineformulation.

That is, the ratio of the weight percent water content to the combinedweight percent glycerine and propylene glycol content of the liquidnicotine formulation may be less than or equal to about 7.

Preferably, the weight percent water content of the liquid nicotineformulation is between about 0.8 times and about 9 times the combinedweight percent glycerine and propylene glycol content of the liquidnicotine formulation. For example, the weight percent water content ofthe liquid nicotine formulation may be between about 0.8 times and about8 times the combined weight percent glycerine and propylene glycolcontent of the liquid nicotine formulation or between about 0.8 timesand about 7 times the combined weight percent glycerine and propyleneglycol content of the liquid nicotine formulation.

More preferably, the weight percent water content of the liquid nicotineformulation is between about 1.5 times and about 9 times the combinedweight percent glycerine and propylene glycol content of the liquidnicotine formulation. For example, the weight percent water content ofthe liquid nicotine formulation may be between about 1.5 times and about8 times the combined weight percent glycerine and propylene glycolcontent of the liquid nicotine formulation or between about 1.5 timesand about 7 times the combined weight percent glycerine and propyleneglycol content of the liquid nicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 2 times and about 9 times the combined weight percentglycerine and propylene glycol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 2 times and about 8 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation or between about 2 times and about 7 timesthe combined weight percent glycerine and propylene glycol content ofthe liquid nicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 3 times and about 9 times the combined weight percentglycerine and propylene glycol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 3 times and about 8 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation or between about 3 times and about 7 timesthe combined weight percent glycerine and propylene glycol content ofthe liquid nicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 4 times and about 9 times the combined weight percentglycerine and propylene glycol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 4 times and about 8 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation or between about 4 times and about 7 timesthe combined weight percent glycerine and propylene glycol content ofthe liquid nicotine formulation.

The weight percent water content of the liquid nicotine formulation maybe between about 5 times and about 9 times the combined weight percentglycerine and propylene glycol content of the liquid nicotineformulation. For example, the weight percent water content of the liquidnicotine formulation may be between about 5 times and about 8 times thecombined weight percent glycerine and propylene glycol content of theliquid nicotine formulation or between about 5 times and about 7 timesthe combined weight percent glycerine and propylene glycol content ofthe liquid nicotine formulation.

Preferably, the liquid nicotine formulation comprises one or morewater-immiscible solvents.

As used herein with reference to the invention, the term“water-immiscible solvent” describes a compound that is liquid at 20° C.and has a water solubility at 20° C. of less than or equal to about 100mg/ml.

Unless stated otherwise, water solubility values recited herein are thewater solubility measured based on the preliminary test of OECD (1995),Test No. 105: Water Solubility, OECD Guidelines for the Testing ofChemicals, Section 1, OECD Publishing, Paris,https://doi.org/10.1787/9789264069589-en. In a stepwise procedure,increasing volumes of distilled water are added at 20° C. to 0.1 g ofthe sample (solid substances must be pulverized) in a 10 mlglass-stoppered measuring cylinder. However, when the substance is anacid, the sample is added to the distilled water in the first step.After each addition of an amount of water, the mixture is shaken for 10minutes and is visually checked for any undissolved parts of the sample.If, after addition of 10 ml of water, the sample or parts of it remainundissolved, the experiment is continued in a 100 ml measuring cylinder.The approximate solubility is given in Table 1 below under that volumeof water in which complete dissolution of the sample occurs.

When the solubility is low, a long time may be required to dissolve asubstance and at least 24 hours should be allowed. If, after 24 hours,the substance is still not dissolved, the measuring cylinder is placedfor at 40° C. in an ultrasound bath for 15 minutes and another 24 hoursallowed (up to a maximum of 96 hours). If the substance is still notdissolved, the solubility is considered to be below the limit value ornot soluble.

TABLE 1 ml of water in which 0.1 g of sample is soluble 0.1 0.5 1 2 10100 >100 Approximate >1000 1000 to 200 to 100 to 50 to 10 to <1solubility 200 100 50 10 1 (mg/ml)

The one or more water-immiscible solvents may advantageously help todissolve and stabilise non-polar components of the liquid nicotineformulation.

The one or more water-immiscible solvents may reduce the hygroscopicityof an aerosol generated from the liquid nicotine formulation when usedin an aerosol-generating system. This may advantageously reduce orprevent increases in the particle or droplet size of the aerosol wheninhaled by a user as a result of adsorption of water in the respiratorytract.

Preferably, the liquid nicotine formulation comprises water and one ormore water-immiscible solvents.

More preferably, the liquid nicotine formulation comprises water, one ormore water-miscible solvents and one or more water-immiscible solvents.

Most preferably, the liquid nicotine formulation comprises water, one ormore water-miscible polyhydric alcohols and one or more water-immisciblesolvents.

When used in an aerosol-generating system, the liquid nicotineformulation generates an aerosol comprising dual-phase particles ordroplets comprising a water-miscible phase and a water-immiscible phase.This may advantageously reduce nicotine adsorption in the upper airwaysand enhance pulmonary nicotine delivery and retention. Without wishingto be bound by theory, the improvement in pulmonary nicotine deliveryand retention is believed to be due to coating or enveloping of thewater-miscible phase by the water immiscible phase. This is believed toreduce nicotine evaporation and adsorption in the upper airways.

Preferably, the liquid nicotine formulation has a water-immisciblesolvent content of greater than or equal to about 1 percent by weight.More preferably, the liquid nicotine formulation has a water-immisciblesolvent content of greater than or equal to about 2 percent by weight.For example, the liquid nicotine formulation may have a water-immisciblesolvent content of greater than or equal to about 4 percent by weight,greater than or equal to about 6 percent by weight or greater than orequal to about 8 percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of less than or equal to about 40 percent by weight.

Preferably, the liquid nicotine formulation has a water-immisciblesolvent content of less than or equal to about 35 percent by weight.More preferably, the liquid nicotine formulation has a water-immisciblesolvent content of less than or equal to about 30 percent by weight. Forexample, the liquid nicotine formulation may have a water-immisciblesolvent content of less than or equal to about 25 percent by weight,less than or equal to about 20 percent by weight or less than or equalto about 15 percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of between about 1 percent by weight and about 40 percent byweight.

Preferably, the liquid nicotine formulation has a water-immisciblesolvent content of between about 1 percent by weight and about 35percent by weight. For example, the liquid nicotine formulation may havea water-immiscible solvent content of between about 1 percent by weightand about 30 percent by weight, between about 1 percent by weight andabout 25 percent by weight, between about 1 percent by weight and about20 percent by weight or between about 1 percent by weight and about 15percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of between about 2 percent by weight and about 40 percent byweight.

More preferably, the liquid nicotine formulation has a water-immisciblesolvent content of between about 2 percent by weight and about 35percent by weight. For example, the liquid nicotine formulation may havea water-immiscible solvent content of between about 2 percent by weightand about 30 percent by weight, between about 2 percent by weight andabout 25 percent by weight, between about 2 percent by weight and about20 percent by weight or between about 2 percent by weight and about 15percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of between about 4 percent by weight and about 40 percent byweight or between about 4 percent by weight and about 35 percent byweight. For example, the liquid nicotine formulation may have awater-immiscible solvent content of between about 4 percent by weightand about 30 percent by weight, between about 4 percent by weight andabout 25 percent by weight, between about 4 percent by weight and about20 percent by weight or between about 4 percent by weight and about 15percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of between about 6 percent by weight and about 40 percent byweight or between about 6 percent by weight and about 35 percent byweight. For example, the liquid nicotine formulation may have awater-immiscible solvent content of between about 6 percent by weightand about 30 percent by weight, between about 6 percent by weight andabout 25 percent by weight, between about 6 percent by weight and about20 percent by weight or between about 6 percent by weight and about 15percent by weight.

The liquid nicotine formulation may have a water-immiscible solventcontent of between about 8 percent by weight and about 40 percent byweight or between about 8 percent by weight and about 35 percent byweight. For example, the liquid nicotine formulation may have awater-immiscible solvent content of between about 8 percent by weightand about 30 percent by weight, between about 8 percent by weight andabout 25 percent by weight, between about 8 percent by weight and about20 percent by weight or between about 8 percent by weight and about 15percent by weight.

Preferably, the one or more water-immiscible solvents comprise one ormore partially water-soluble solvents.

As used herein with reference to the invention, the term “partiallywater-soluble solvent” describes a compound that is liquid at 20° C. andhas a water solubility at 20° C. of between about 20 mg/ml and about 100mg/ml.

The one or more partially water-soluble solvents may have a maximumcarbon chain length of less than or equal to 12. For example, the one ormore partially water-soluble solvents may have a maximum carbon chainlength of less than or equal to 10.

Suitable partially water-soluble solvents include, but are not limitedto polysorbate 80, triacetin and triethyl citrate.

Preferably, the one or more water-immiscible solvents comprise one ormore water-insoluble solvents.

As used herein with reference to the invention, the term“water-insoluble solvent” describes a compound that is liquid at 20° C.and has a water solubility at 20° C. of less than or equal to about 5mg/ml.

The one or more water-insoluble solvents may have a maximum carbon chainlength of less than or equal to 30. For example, the one or morewater-insoluble solvents may have a maximum carbon chain length of lessthan or equal to 20, less than or equal to 18, less than or equal to 16,less than or equal to 14 or less than or equal to 12.

Suitable water-insoluble solvents include, but are not limited to oleicacid and MIGLYOL® (mixture of decanoyl- and octanoyl glycerides).

More preferably, the one or more water-immiscible solvents comprise oneor more partially water-soluble solvents and one or more water-insolublesolvents.

Preferably, the liquid nicotine formulation comprises one or morewater-soluble organic acids.

As used herein with reference to the invention, the term “water-solubleorganic acid” describes an organic acid having a water solubility at 20°C. of greater than or equal to about 500 mg/ml.

The one or more water-soluble organic acids may advantageously bindnicotine in the liquid nicotine formulation through formation of one ornicotine salts.

In embodiments in which the liquid nicotine formulation comprises waterand one or more water-miscible solvents, the one or more nicotine saltsmay advantageously be dissolved and stabilised in the water and one ormore water-miscible solvents. In embodiments in which the liquidnicotine formulation comprises water, one or more water-misciblesolvents and one or more water-immiscible solvents, this mayadvantageously reduce nicotine adsorption in the upper airways andenhance pulmonary nicotine delivery and retention as discussed above.

More preferably, the liquid nicotine formulation comprises one or morewater-soluble carboxylic acids.

Suitable water-soluble carboxylic acids include, but are not limited to,acetic acid, citric acid, lactic acid, levulinic acid, malic acid,malonic acid and pyruvic acid.

Most preferably, the liquid nicotine formulation comprises lactic acid.

Preferably, the liquid nicotine formulation has a water-soluble organicacid content of greater than or equal to about 2 percent by weight. Morepreferably, the liquid nicotine formulation has a water-soluble organicacid content of greater than or equal to about 3 percent by weight.

Preferably, the liquid nicotine formulation has a water-soluble organicacid content of less than or equal to about 8 percent by weight. Morepreferably, the liquid nicotine formulation has a water-soluble organicacid content of less than or equal to about 6 percent by weight.

Preferably, the liquid nicotine formulation has a water-soluble organicacid content of between about 2 percent by weight and about 8 percent byweight. For example, the liquid nicotine formulation may have awater-soluble organic acid content of between about 2 percent by weightand about 6 percent by weight.

More preferably, the liquid nicotine formulation has a water-solubleorganic acid content of between about 3 percent by weight and about 8percent by weight. For example, the liquid nicotine formulation may havea water-soluble organic acid content of between about 2 percent byweight and about 6 percent by weight.

The liquid nicotine formulation may be a substantially uncaffeinatedliquid nicotine formulation.

As used herein with reference to the invention, the term “substantiallyuncaffeinated liquid nicotine formulation” describes a liquid nicotineformulation having a caffeine content of less than 0.5 percent byweight. For example, the liquid nicotine formulation may have a caffeinecontent of less than about 0.4 percent by weight, less than about 0.3percent by weight or less than about 0.2 percent by weight.

The liquid nicotine formulation may be a substantially caffeine-freeliquid nicotine formulation.

As used herein with reference to the invention, the term “substantiallycaffeine-free liquid nicotine formulation” describes a liquid nicotineformulation having a caffeine content of less than about 0.1 percent byweight.

The liquid nicotine formulation may be a caffeine-free liquid nicotineformulation.

As used herein with reference to the invention, the term “caffeine-freeliquid nicotine formulation” describes a liquid nicotine formulationhaving a caffeine content of 0 percent by weight.

As used herein with reference to the invention, the term “caffeine”describes caffeine or a caffeine salt. When referring to a caffeinesalt, the amounts of caffeine recited herein are the amount of caffeinecation.

The liquid nicotine formulation may comprise one or more flavourants.Suitable flavourants include, but are not limited to, menthol.

Preferably, the liquid nicotine formulation has a flavourant content ofless than or equal to about 4 percent by weight. More preferably, theliquid nicotine formulation has a flavourant content of less than orequal to about 3 percent by weight.

According to the invention there is also provided a cartridge for use inan aerosol-generating system, the cartridge containing a liquid nicotineformulation according to the invention.

The cartridge may comprise an atomiser configured to generate an aerosolfrom the liquid nicotine formulation.

A cartridge containing the liquid nicotine formulation and an atomiserconfigured to generate an aerosol from the liquid nicotine formulationmay be referred to as a “cartomiser”.

The atomiser may be a thermal atomiser.

As used herein with reference to the invention, the term “thermalatomiser” describes an atomiser that is configured to heat the liquidnicotine formulation to generate an aerosol.

In embodiments in which the cartridge comprises a thermal atomiser, inuse heating of the liquid nicotine formulation by the atomiser increasesthe temperature of the liquid nicotine formulation. This may reduce theviscosity of the liquid nicotine formulation and facilitate generationof an inhalable aerosol having a small particle or droplet size. Thismay advantageously enhance pulmonary nicotine delivery and retention.

The cartridge may comprise any suitable type of thermal atomiser.

The thermal atomiser may comprise a heater and a liquid transportelement configured to transport liquid nicotine formulation to theheater.

The liquid transport element may comprise a capillary wick. The heatermay comprise a heater coil.

The thermal atomiser may comprise an electric heater. For example, thethermal atomiser may comprise an electric heater comprising a resistiveheating element or an inductive heating element.

Preferably, the atomiser is a non-thermal atomiser.

As used herein with reference to the invention, the term “non-thermalatomiser” describes an atomiser that is configured to generate anaerosol from the liquid nicotine formulation by means other thanheating.

In embodiments in which the cartridge comprises a non-thermal atomiser,in use the temperature of the liquid nicotine formulation is notsignificantly increased. Consequently, it is particularly advantageousin such embodiments for the liquid nicotine formulation to have aviscosity at 20° C. of less than or equal to about 20 mPa·s.

The cartridge may comprise any suitable type of non-thermal atomiser.

For example, the non-thermal atomiser may be an impinging jet atomiser,an ultrasonic atomiser or a vibrating mesh atomiser.

According to the invention there is further provided anaerosol-generating system comprising a liquid nicotine formulationaccording to the invention and an atomiser configured to generate anaerosol from the liquid nicotine formulation.

The atomiser may be a thermal atomiser.

The aerosol-generating system may comprise any suitable type of thermalatomiser.

The thermal atomiser may comprise a heater and a liquid transportelement configured to transport liquid nicotine formulation to theheater.

The liquid transport element may comprise a capillary wick. The heatermay comprise a heater coil.

The thermal atomiser may comprise an electric heater. For example, thethermal atomiser may comprise an electric heater comprising a resistiveheating element or an inductive heating element.

Preferably, the atomiser is a non-thermal atomiser.

The aerosol-generating system may comprise any suitable type ofnon-thermal atomiser.

For example, the non-thermal atomiser may be an impinging jet atomiser,an ultrasonic atomiser or a vibrating mesh atomiser.

The aerosol-generating system may comprise: a cartridge according to theinvention containing the liquid nicotine formulation; and anaerosol-generating device comprising a housing defining a device cavityconfigured to receive at least a portion of the cartridge.

The aerosol-generating system may comprise: a consumable cartridgeaccording to the invention containing the liquid nicotine formulation;and a reusable aerosol-generating device comprising a housing defining adevice cavity configured to receive at least a portion of the cartridge.

The aerosol-generating device may comprise a battery and controlelectronics.

The aerosol-generating system may comprise: a cartridge according to theinvention containing the liquid nicotine formulation and the atomiser;and an aerosol-generating device comprising a housing defining a devicecavity configured to receive at least a portion of the cartridge.

The aerosol-generating system may comprise: a cartridge according to theinvention containing the liquid nicotine formulation; and anaerosol-generating device comprising a housing defining a device cavityconfigured to receive at least a portion of the cartridge and theatomiser.

For the avoidance of doubt, features described above in relation to oneaspect of the invention may also be applicable to other aspects of theinvention. In particular, features described above in relation to theliquid nicotine formulation of the invention may also relate, whereappropriate, to the cartridge of the invention and theaerosol-generating system of the invention. Similarly, featuresdescribed above in relation to the cartridge of the invention may alsorelate, where appropriate, to the aerosol-generating system of theinvention, and vice versa.

Embodiments of the invention will now be described, by way of exampleonly, with reference to the following examples and accompanyingdrawings, in which:

FIGS. 1A and 1B show the aerodynamic size distribution of aerosolsgenerated from a liquid nicotine composition according to the inventionusing four aerosol-generating systems comprising non-thermal atomisers.

EXAMPLES

Four liquid nicotine formulations according to the invention (ExamplesA, B, C and D) were prepared having the viscosities and compositionsshown in Table 2. For comparison, a liquid formulation not according tothe invention (Example E) was also prepared having the viscosity andcomposition shown in Table 2.

TABLE 2 Example A B C D E Viscosity 2 4 6 9 29 (mPa s) Nicotine 2.7 2.72.7 2.7 0 (% by weight) Water 80 60 60 40 20 (% by weight) Vegetablewater-miscible 8.7 25 25 45 40 Glycerine polyhydric alcohol (% byweight) Propylene Glycol 1.5 4.2 4.2 4.2 40 (% by weight) Triacetinpartially water- 0.9 2 2 2 0 (% by weight) soluble solvent TriethylCitrate 2 2 10 2 0 (% by weight) Lactic Acid water-soluble 4.3 4.3 4.34.3 0 (% by weight) organic acid

Aerosols were generated from the liquid nicotine composition accordingto the invention of Example A using the four aerosol-generating systemscomprising non-thermal atomisers shown in Table 3. The aerodynamic sizedistributions of the aerosols were measured using an AerodynamicParticle Sizer® (APS™) Model 3321 spectrometer from TSI Incorporated.The results are shown in FIGS. 1A and 1B.

TABLE 3 Example Non-thermal aerosol-generating system Example A1Impinging jet nebulizer (nozzle opening: 10 micrometres; driving force:51N) Example A2 OMRON Healthcare MicroAIR U100 passive mesh nebulizer(driven by 50 Vpp at 177 kHz with 2 Hz modulation; mesh hole diameter:about 4 micrometres; mesh hole to hole distance about 60 micrometres)Example A3 Air Wick ® Essential Mist Diffuser active mesh nebulizer(120-180 kHz; mesh hole diameter: 4-8 micrometres) Example A4 SurfaceAcoustic Wave (SAW) device (double engine operation with each sidedriven by 600 mVpp at 42.122 MHz with 500 Hz modulation)

FIG. 1A shows the differential mass concentration (dM) againstaerodynamic diameter (APS diameter) of the aerosols and FIG. 1B showsthe particle differential number concentration (dN) against aerodynamicdiameter (APS diameter) of the aerosols.

As shown by FIGS. 1A and 1B, use of the liquid nicotine compositionaccording to the invention of Example A in the four aerosol-generatingsystems advantageously generates aerosols exhibiting a small dropletsize.

1.-15. (canceled)
 16. A liquid nicotine formulation for anaerosol-generating system, the liquid nicotine formulation comprising:glycerine and having a viscosity at 20° C. of less than or equal toabout 20 mPa·s, wherein the liquid nicotine formulation is asubstantially uncaffeinated liquid nicotine formulation, and wherein theliquid nicotine formulation has a glycerine content of greater than orequal to about 6 percent by weight.
 17. The liquid nicotine formulationaccording to claim 16, wherein the liquid nicotine formulation has aviscosity at 20° C. of less than or equal to about 12 mPa·s.
 18. Theliquid nicotine formulation according to claim 16, wherein the liquidnicotine formulation has a viscosity at 20° C. of greater than or equalto about 1 mPa·s.
 19. The liquid nicotine formulation according to claim16, further comprising water, wherein the liquid nicotine formulationhas a water content of greater than or equal to about 30 percent byweight.
 20. The liquid nicotine formulation according to claim 19,wherein a weight percent water content of the liquid nicotineformulation is at least about 0.8 times a weight percent water-misciblesolvent content of the liquid nicotine formulation.
 21. The liquidnicotine formulation according to claim 18, further comprising one ormore water-immiscible solvents having a water solubility at 20° C. ofless than or equal to about 100 mg/ml, wherein the liquid nicotineformulation has a water-immiscible solvent content of greater than orequal to about 2 percent by weight.
 22. The liquid nicotine formulationaccording to claim 21, wherein the one or more water-immiscible solventscomprise one or more partially water-soluble solvents having a watersolubility at 20° C. of between about 20 mg/ml and about 100 mg/ml. 23.The liquid nicotine formulation according to claim 22, wherein the oneor more water-immiscible solvents comprise one or more water-insolublesolvents having a water solubility at 20° C. of less than or equal toabout 5 mg/ml.
 24. The liquid nicotine formulation according to claim18, further comprising one or more water-soluble organic acids, whereinthe liquid nicotine formulation has a water-soluble organic acid contentof greater than or equal to about 2 percent by weight.
 25. A cartridgefor an aerosol-generating system, the cartridge containing a liquidnicotine formulation according to claim
 16. 26. The cartridge accordingto claim 25, further comprising an atomiser configured to generate anaerosol from the liquid nicotine formulation.
 27. An aerosol-generatingsystem, comprising: a liquid nicotine formulation according to claim 16;and an atomiser configured to generate an aerosol from the liquidnicotine formulation.
 28. The cartridge according to claim 26, whereinthe atomiser is a non-thermal atomiser.
 29. The aerosol-generatingsystem according to claim 27, wherein the atomiser is a non-thermalatomiser.
 30. The cartridge according to claim 26, wherein the atomiseris a thermal atomiser comprising a heater and a liquid transport elementconfigured to transport liquid nicotine formulation to the heater. 31.The aerosol-generating system according to claim 27, wherein theatomiser is a thermal atomiser comprising a heater and a liquidtransport element configured to transport liquid nicotine formulation tothe heater.